Abstract P3-06-18: Comprehensive genomic profiling of carcinosarcomas of the breast

Abstract

Abstract Background: Carcinosarcomas of the breast (BCSC) are exceptionally rare and the underlying genomic drivers are still being elucidated. Comprehensive genomic profiling (CGP) determines the tumor mutation burden (TMB) and identifies all four classes of genomic alterations (GA) that have potential to direct personalized treatment strategies. Methods: CGP by hybridization capture of exons from up to 315 cancer-related genes and select introns of 28 genes commonly rearranged in cancer was applied to ≥ 50ng of DNA extracted from 9 consecutive BCSC and sequenced to high, uniform median coverage (>500X). Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined by principal components analysis of optimized loci. Results: The 9 BCSC patients had a median age of 57 yrs (range 49-78 yrs). CGP was performed on the primary BCSC in 4 cases and on metastasis biopsies in 5 cases (4 lung and 1 lymph node). The mean GA/tumor was 6.6 and clinically relevant GA (CRGA)/tumor was 1.3. The most frequent non-CRGA were in TP53 (89%), MYC (56%) and LYN (40%). The most frequent CRGA were in PIK3CA (33%), and NF1, BRCA1, PTEN, RICTOR, FGFR1, AKT2 and STK11 (all at 11%). The median TMB for all BCSC was 2.4 mut/Mb with 1 (11%) tumor with a TMB > 20 mut/Mb and 8 BCSC (88%) with TMB < 5 mut/Mb. Five of 5 BCSC (100%) that were available for MSI status testing were microsatellite stable. Conclusions: On CGP, BCSC feature a high frequency of GA, but only a modest frequency of CRGA and high TMB. However, when the CRGA and TMB positive cases are combined (77.8% overall in this series), the opportunity for personalized targeted and immunotherapies are significant. Thus, further investigation of precision therapies for BCSC in the clinical trial setting appear warranted. Citation Format: Gay LM, Elvin JA, Vergilio J-A, Killian JK, Ramkissoon S, Severson E, Daniel S, Hammerich A, Sokol E, Frampton G, Chung J, Trabucco S, Ali S, Reddy P, Schrock AB, Miller VA, Ross JS. Comprehensive genomic profiling of carcinosarcomas of the breast [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-06-18.